Eph A10-modified pH-sensitive liposomes loaded with novel triphenylphosphine-docetaxel conjugate possess hierarchical targetability and sufficient antitumor effect both in vitro and in vivo.
Eph A10-modified pH-sensitive liposomes loaded with novel triphenylphosphine-docetaxel conjugate possess hierarchical targetability and sufficient antitumor effect both in vitro and in vivo.
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Eph A10修饰的pH敏感脂质体负载新型三苯基膦-多西紫杉醇缀合物，在体外和体内均具有分级靶向性和足够的抗肿瘤作用。
DOI：
10.1080/10717544.2018.1446475
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Zhao X
中科院分区：
文献类型：
--
作者：
Zhang J;Yang C;Pan S;Shi M;Li J;Hu H;Qiao M;Chen D;Zhao X
线粒体靶向治疗被认为是一种有效治疗癌症的有前途的方法，但正电荷诱导的非特异性细胞毒性严重限制了其应用。为了克服这一缺点，成功合成了一种新型的线粒体靶向偶联物三苯基膦-多西他赛（TD），并将其掺入脂质体（EPSLP/TD）中，该偶联物具有良好的pH敏感性、EphA 10介导的主动靶向性以及靶向EphA的能力。EPSLP/TD具有粒径小、包封率高、pH敏感性好等特点。与载药脂质体（EPSLP/DTX）相比，EPSLP/TD对MCF-7细胞具有更高的细胞毒活性。线粒体靶向实验表明，三苯膦（TPP）能有效地将DTX靶向线粒体。Western免疫印迹实验表明，EPSLP/TD能有效地将抗肿瘤药物转运至线粒体，并通过线粒体介导的凋亡途径诱导细胞凋亡。体内抗肿瘤实验表明EPSLP/TD具有良好的体内抗肿瘤活性。组织学检测显示EPSLP/TD具有较强的诱导凋亡、抗增殖和抗血管生成作用。本工作探讨了分级靶向pH敏感脂质体作为一种合适的载体用于肿瘤治疗的可能性。
Mitochondrial-targeting therapy was considered to be a promising approach for the efficient treatment of cancer while positive charge induced nonspecific cytotoxicity severely limits its application. To overcome this drawback, a novel mitochondria targeted conjugate triphenylphosphine-docetaxel (TD) has been synthesized successfully and incorporated it into liposomes (EPSLP/TD), which possessed excellent pH-sensitive characteristic, EphA 10 mediated active targetability as well as mitochondria-targeting capability. EPSLP/TD was characterized to have a small particle size, high-encapsulation efficiency and excellent pH-sensitive characteristic. Compared with DTX-loaded liposomes (EPSLP/DTX), EPSLP/TD possessed higher cytotoxicity against MCF-7 cell line. Mitochondrial-targeting assay demonstrated mitochondria-targeting moiety triphenylphosphine (TPP) could efficiently deliver DTX to mitochondria. Western immunoblotting assay indicated that EPSLP/TD could efficiently deliver antitumor drug to mitochondria and induce cell apoptosis via mitochondria-mediated apoptosis pathway. In vivo antitumor study demonstrated EPSLP/TD owed excellent in vivo antitumor activity. Histological assay demonstrated EPSLP/TD showed strongly apoptosis inducing effect, anti-proliferation effect and anti-angiogenesis effect. This work investigated the potential of hierarchical targeting pH-sensitive liposomes is a suitable carrier to activate mitochondria-mediated apoptosis pathway for cancer therapy.
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DOI：
10.1016/j.jconrel.2015.08.050
发表时间：
2015-12-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Du J;Lane LA;Nie S
通讯作者：
Nie S
影响因子：
8.4
作者：
Aziz, Ayman A. Abdel;Seda, Sabry H.;Mohammed, Soha F.
通讯作者：
Mohammed, Soha F.
具有可脱落 PEG 壳的还原敏感胶束，由 Y 形两亲性聚合物自组装而成，用于细胞内阿霉素释放
影响因子：
5.8
作者：
Cui, Can;Yu, Ping;Huang, Shi-Wen
通讯作者：
Huang, Shi-Wen
开发靶向氯尼达明脂质体，通过作用于线粒体信号通路来规避耐药癌症
影响因子：
14
作者：
Li, Nan;Zhang, Cheng-Xiang;Lu, Wan-Liang
通讯作者：
Lu, Wan-Liang
影响因子：
3.5
作者：
Li, Yue;Bhindi, Ravinay;Khachigian, Levon M.
通讯作者：
Khachigian, Levon M.